In Field asymmetric waveform ion mobility spectrometry (FAIMS), also termed differential mobility spectrometry (DMS), ions are separated in gases by the difference of mobility at two substantially unequal electric field intensities, E (R. Guevremont. J. Chromatogr. A 2004, 1058, 3). The gas pressure is typically ambient (atmospheric), though operation at reduced pressure is possible and may be advantageous (E. G. Nazarov, S. L. Coy, E. V. Krylov, R. A. Miller, G. A. Eiceman. Anal. Chem. 2006, 78, 7697). FIG. 1a shows a flow-driven FAIMS stage 50, where ions are filtered in the analytical gap 12 between two electrodes 10, one carrying a periodic asymmetric high-voltage waveform V(t) 18 with the amplitude termed the “dispersion voltage” (DV) and the same or other electrode carrying a fixed “compensation voltage” (CV) 8. At any given CV, only species with a particular difference between the mobility at “high” and “low” E in the positive and negative V(t) segments remains in equilibrium and is most likely to pass the gap. In the FAIMS systems reduced to practice so far, ions are moved through the gap by a steady laminar flow of carrier gas 4. Besides stand-alone use, FAIMS is increasingly employed to filter ions prior to mass spectrometry (MS) and/or drift tube ion mobility spectrometry (DTIMS) analyses (R. W. Purves, R. Guevremont. Anal. Chem. 1999, 71, 2346; K. Tang, F. Li, A. A. Shvartsburg, E. F. Strittmatter, R. D. Smith. Anal. Chem. 2005, 77, 6381). Ions can be propelled through the gap by a relatively weak electric field (EL) along it instead of the flow (U.S. Pat. No. 7,456,390, U.S. Pat. No. 7,547,879). In FIG. 1b, such a longitudinal field-driven FAIMS stage 50 is shown with EL along the analytical gap 12 established by segmenting both electrodes 10 and applying a voltage ladder to the segments. Alternatively, the field EL may be created by maintaining a voltage drop across contiguous electrodes with substantial ohmic resistance, as is known in the art of DTIMS (M. Kwasnik, K. Fuhrer, M. Gonin, K. Barbeau, F. M. Fernandez. Anal. Chem. 2007, 79, 7782) and has been considered for FAIMS (U.S. Pat. No. 7,498,570).
As a filtering technique, FAIMS inherently involves ion losses. Hence, to maximize the sensitivity of multidimensional analytical platforms comprising FAIMS, one needs to switch it “off”, i.e., to employ the other stage(s) without FAIMS filtering. In particular, the ability to use FAIMS/MS systems for MS-only analyses is usually desired. As FAIMS normally precedes MS or other stage(s) in hybrid systems, this means effectively transmitting ions to those stage(s) through or around the FAIMS unit. In the current art, effective use of such other stage(s) without FAIMS requires physically removing the FAIMS unit and reassembling the instrument in a new configuration. This process calls for trained personnel, testing, and recalibration of the instrument after each insertion or removal of a FAIMS stage, at a substantial cost in time and resources. Ions still pass FAIMS with the asymmetric waveform and CV switched off, but the transmission is poor because of large losses due to diffusion and Coulomb repulsion in a narrow analytical gap. Such losses decrease the sensitivity of instrument platforms without FAIMS, typically to unacceptable levels. Accordingly, there is a need for capability to switch off the FAIMS separation in hybrid platforms without significantly diminishing the instrument sensitivity.
In flow-driven FAIMS, all species traverse the gap in the same time defined by the flow speed and gap length. As the low-field (isotropic) diffusion coefficient of an ion D0 is proportional to mobility K by the Einstein law, species with higher K values diffuse faster and thus spread farther in equal time. Second, more mobile ions further experience stronger field heating that increases the diffusion coefficient, and especially its longitudinal component DII (along the separation field) that determines ion loss on electrodes, above D0. Third, as the amplitude of ion oscillation in the V(t) cycle also scales with K, more mobile species undergo wider oscillations that effectively constrain the gap. These three factors add to a pronounced discrimination against more mobile ions, which are preferentially lost in a gap of any geometry. This is unrelated to the discrimination based on the K(E) form that occurs in curved gaps only (A. A. Shvartsburg, R. D. Smith. J. Am. Soc. Mass Spectrom. 2007, 9, 1672). This effect distorts the FAIMS spectra, complicating quantification, affecting the measured isomer abundances, and reducing the sensitivity and reliable dynamic range. Same effect decreases the FAIMS resolution for less mobile species, resulting in a non-uniform and sub-optimum resolving power over a spectrum. For a complex sample that comprises ions with a wide range of K, the discrimination may be severe enough to suppress more mobile species below the detection limit, precluding their observation in FAIMS, and prevent the resolution of different less mobile species that could otherwise be separated. As FAIMS is applied to increasingly complex proteomic and other biological samples that include more diverse species, the issue of mobility discrimination becomes more topical.
In field-driven FAIMS, the ion residence time in the gap (tres) scales as 1/K and more mobile ions exit the gap faster. This offsets the proportionality of D0 to K such that all ions would experience identical diffusional broadening at the FAIMS exit (assuming isotropic diffusion), but not the other two factors that contribute to the mobility-based discrimination in flow-driven FAIMS as described above. Therefore, the transition from flow- to field-driven FAIMS should ameliorate, but not eliminate, the generally unwanted suppression of ions with higher K values (A. A. Shvartsburg, R. D. Smith. J. Am. Soc. Mass Spectrom. 2007, 9, 1672). The remaining discrimination, still significant in simulations, will be adverse to many applications. Accordingly, one would desire a FAIMS system that reduces this discrimination further.